Project description:To explore the classification and functional roles of bladder immune cells during urinary tract infection (UTI), we performed scRNA-seq analysis of immune cells extracted from mouse bladders.
Project description:Obesity is a significant public health concern associated with increased infection risk, but the mechanisms remain unclear. Using a diet induced obesity mouse model, we investigate how obesity impacts urinary tract infection (UTI) susceptibility and bladder urothelial defenses. High fat diet-fed female and male C57BL/6 mice exhibit increased susceptibility to uropathogenic E. coli (UPEC) following experimental UTI. Transcriptomic analysis of bladder urothelial cells reveals sex-specific gene expression changes, but both sexes share activation of focal adhesion and extracellular matrix signaling. Western blot and immunostaining confirm activation of focal adhesion kinase (FAK), a central component of the focal adhesion pathway, in the bladders of obese female and male mice. Mechanistically, primary human urothelial cells overexpressing FAK exhibit increased UPEC invasion. These findings demonstrate that obesity enhances UTI susceptibility and identify FAK as a conserved pathway disrupted by obesity, contributing to increased UPEC vulnerability.
Project description:Resident macrophages are highly abundant in the bladder, playing key roles in directing immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and precisely how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders with distinct localization, protein expression, and transcriptomes. Using a model of urinary tract infection, we validated our transcriptomics analyses finding that one macrophage subset phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the other subset died rapidly after infection. After resolution of infection, tissue-resident macrophage subsets were partially replaced by monocyte-derived cells with distinct transcriptional profiles. Elimination of these macrophages led to a type 1 biased immune response to challenge infection. Our study brings considerably more knowledge about the biology of bladder resident macrophages and their response to primary and recurrent infection, which may have broader implications for macrophage subsets in other mucosal tissues.